MRNA anti-cancer vaccine, Moderna trials on melanoma have begun: what we know – breaking latest news

The RNA-based technology, made famous by the anti-Covid vaccines, is also beginning to be concretely tested against tumors. An experimental anti-cancer vaccine by Modernwhich he uses mRNAtogether with the immunotherapy drug pembrolizumab, from Merck, has given encouraging results against melanoma.

I test were performed on 157 patients with stage 3 or 4 melanoma who had already undergone surgery. Some of them were given nine doses of Moderna’s investigational cancer vaccine along with pembrolizumab every three weeks for a year. Others received only pembrolizumab.

I results indicated that the combination of the two agents reduced the risk of relapse or mortality by 44% compared with immunotherapy alone. Phase 3 trials, the ones decisive for eventual approval by regulatory agencies, should begin next year and will probably also involve other types of cancers.

It was known that the mRNA technique would be used to tackle many diseases against which we have no effective weapons today. In fact, mRNAs can be guided to become vaccines or drugs through interaction with other molecules.

What is mRNA

In the genome, in the case of man a book with about three billion two hundred million letters, there are genes, the units of information for the functioning of our organism; the alphabet in which they are written has four letters, G, A, C and T.
RNA uses the same language as DNA but instead of T it uses U. The DNA of the genome is therefore translated messenger RNA, so called precisely because it carries a message: it works like a computer’s punched card and allows for the translation of genetic information, encoded in the language of DNA, into proteins, written in yet another language, in which the letters that’s 20 amino acids.

Transcription and translation

There are 25,000 genes, but they are not all transcribed and then translated, everywhere: about 5,000 are translated in each cell and different genes are expressed and translated in different tissues. The proteins that a brain cell needs are different from those that make a heart cell work and it is the mRNAs that decide which genes must be translated into the proteins needed from time to time.
The attempt to interfere with mRNAs has been going on for many years but RNA degrades quickly, making it difficult to manipulate in the laboratory. Furthermore, it is immediately eliminated by our body, which sees it as a danger signal, and not a coincidence, because many viruses have an RNA genome. Injecting an mRNA as such to interfere with biological processes is therefore impossible, because it does not ‘survive’ long enough to exert an effect. In 2005, however, it was discovered that it is possible to avoid the alarm signal towards RNA by replacing the letter U of its alphabet with a slightly different fake -U: thus the immune system no longer considers an external mRNA as an enemy, which can act in cells as a vaccine, if it brings information to the body to produce proteins of a germ against which an immune response is desired, or a drug, if it causes missing or deficient proteins to be produced or if it interferes with the genome translation process.

The strategy

All the drugs available today target no more than a thousand proteins, i.e. no more than a thousand genes out of the total of 25,000 coding; instead, using mRNA-based technologies means being able to interact with any gene. It is enough to know the sequence of the target gene, which leads to an unwanted protein responsible for a disease, to a protein that the immune system must recognize or to a missing or deficient protein, to create an mRNA in a test tube which, in the first case, matches the one causes the wrong protein to be produced, thus effectively and super-precisely inactivating the molecule; in the second case it carries the information to produce the protein and make it known to the immune system; in the third, it becomes the mold on which to produce the protein you need.